Project summary Brain is a remarkably plastic organ which is not only shaped by the genetic programs that are executed as developmental processes, but also by the enduring influences of various environmental milieu, including behavioral experiences and memory formation. As a result, it has been proven challenging to reveal the brain- wide causal structure-function relationships, which is a prerequisite for rationally designed brain repair strategies. Indeed, most brain diseases, including psychiatric and neurological disorders, still remain only partially treatable. This proposal aims to address these challenges by developing a foundational framework for simplifying the brain architectural complexity as composition of over-represented motifs and patterns, and their plasticity across individuals and across brain regions. Such partitioning of architectural features space will enable the brain-wide mapping of causal structure-function relationships, and hence facilitate the development of better diagnosis and treatments. The basic premise of the proposal involves high-content multi-scale sampling of features from a large number of brains, and their classification, using state-of-the-art computational geometry and graph re- normalization multi-scaling approaches, into constant development-dependent and variable experience- dependent components. These resources and knowledge-base will enable precise quantitative characterization of the causal basis of various brain disorders to facilitate development of effective treatments. The proposed research is very well suited to the objectives of the New Innovator program. The project involves development of enabling highly inter-disciplinary technologies, as well as their applications to understand the basic principles of brain organization and function. My inter-disciplinary training in developmental biology, evolutionary biology, neuroscience, optical engineering and data analytics, together with my demonstrated success in intact brain structure and function mapping studies uniquely enables me to take on this ambitious long-term task of brain- wide mapping of causal structure-function relationships.